Transforming growth factors (TGF) are a subset of a larger group of polypeptide growth factors. They differ from other growth factors in that they are able to induce non-neoplastic cells to grow in anchorage-independent fashion in soft agar medium. However, the physiological role of TGF is not understood. In a preliminary experiment we had observed that a crude preparation of TGF from bovine kidney extract (obtained from Dr. A. Roberts, NCI) induced hyperplastic alveolar nodule-like lesions, similar to those induced by carcinogen, in mouse mammary gland organ culture. We propose to investigate the interactions of TGF alpha or TGF-1 and TGF beta or TGF-11 on the development of module- like lesions. Furthermore, the cells prepared from TGF-treated glands will be transplanted into gland-free fat pads of the syngeneic mice to determine if TGF-induced lesions are capable of forming mammary tumors. The role of hormones and retinoids in chemically-induced mammary carcinogenesis is well established, however, their interactions with the endogeneous growth factors implicated in transformation is not known. We propose to investigate the effects of hormones and retinoids on the TGF-induced alterations in mammary gland physiology in vitro. The results will indicate whether retinoids or hormones can modulate TGF action. In summary, this application is planned to focus on a problem whether TGF has any physiological role in mammary carcinogenesis. Secondly, whether retinoids and/or hormones, which are known to have a significant role in mammary carcinogenesis, influence TGF-induced changes. And, finally, a testable hypothesis is proposed to understand the interactions of retinoid, hormone and TGF on mammary tissues.